Alavi A, Arden N, Spector T D, Axford J S
Academic Unit for Musculoskeletal Diseases, St. George's Hospital Medical School, London, UK.
J Rheumatol. 2000 Jun;27(6):1379-85.
To determine whether clinical outcome during pregnancy in rheumatoid arthritis (RA) is associated with changes in the levels of exposed immunoglobulin G (IgG) terminal sugars.
Serum IgG glycosylation from 23 pregnant patients with RA was analyzed during the prenatal, antenatal, and post-partum periods. Patients were randomly selected on the basis of whether they achieved spontaneous remission (n = 11) or did not remit (n = 12); of the latter group 6 patients experienced a relapse in disease activity. Levels of exposed terminal IgG sugars, galactose (Gal), N-acetylglucosamine (GlcNAc), and sialic acid (SA), were estimated in a lectin binding assay using Ricinis (communis, Bandeiraea simplicifolia II, and Sambucus nigra, respectively.
Exposed Gal levels increased (p<0.02) and GlcNAc levels decreased (p<0.05) in the antenatal period, and returned to preconception levels during post-partum. GlcNAc rebound was instantaneous (p<0.005), whereas Gal remained high for a further 10 weeks. SA did not undergo any major changes. Remission was associated with an earlier and significantly greater antenatal reduction in GlcNAc (2nd and 3rd trimester; p<0.02) in comparison to the groups that did not experience a decrease in disease activity. Analysis of individual IgG samples during the first trimester revealed a significant negative correlation between Gal and GlcNAc in the remission group (r = -0.80; p<0.05), which was opposite to that found in the relapse group (r = +0.87; p<0.03). There was no significant difference between the groups with regard to the timing and/or incidence of a post-partum flare of disease.
Temporal changes in the levels of IgG terminal sugars, in particular exposed GlcNAc, are integrally associated with the clinical manifestation of RA in pregnancy. Generation of IgG sugar micro-heterogeneity is complex and understanding it may help unravel pathogenic features associated with RA.
确定类风湿关节炎（RA）患者孕期的临床结局是否与暴露的免疫球蛋白G（IgG）末端糖水平的变化相关。
对23例孕期RA患者在产前、产中及产后的血清IgG糖基化进行分析。根据患者是否实现自发缓解（n = 11）或未缓解（n = 12）进行随机选择；后一组中有6例患者疾病活动复发。使用蓖麻（分别为蓖麻、单叶相思子和黑接骨木）凝集素结合试验估计暴露的末端IgG糖、半乳糖（Gal）、N-乙酰葡糖胺（GlcNAc）和唾液酸（SA）的水平。
产前暴露的Gal水平升高（p<0.02），GlcNAc水平降低（p<0.05），产后恢复到孕前水平。GlcNAc的反弹是即时的（p<0.005），而Gal在接下来的10周内仍保持高水平。SA没有发生任何重大变化。与疾病活动未降低的组相比，缓解与产前GlcNAc更早且显著更大程度的降低相关（孕中期和孕晚期；p<0.02）。对孕早期个体IgG样本的分析显示，缓解组中Gal和GlcNAc之间存在显著负相关（r = -0.80；p<0.05），这与复发组中的情况相反（r = +0.87；p<0.03）。产后疾病 flare 的时间和/或发生率在各组之间没有显著差异。
IgG末端糖水平的时间变化，特别是暴露的GlcNAc水平变化，与RA孕期临床表现密切相关。IgG糖微异质性生成复杂，了解其有助于揭示与RA相关疾病特征。
